Despite the numerous reports on the successful results of ACL reconstruction, upwards of 40% of ACL reconstruction patients have abnormal laxity and undergo revision surgery. Moreover, ACL reconstruction does not reduce the rate of osteoarthritis when compared to more conservative treatments. There is little quantitative data demonstrating how ACL deficiency alters in-vivo knee kinematics in six degrees-of-freedom (6DOF) and how the contemporary ACL reconstruction restores the altered knee kinematics in 6DOF under in-vivo physiological loading conditions. Further, no data has been reported on how the combined meniscal injury will affect the in-vivo function of the ACL reconstructed knees. The first aim of this project is to compare the in-vivo biomechanics of healthy and acute ACL-injured knees within the same subject using a novel imaging technique. Three-dimensional (3D) knee models of human subjects will be created from MR images. These models will then be matched to a series of dual fluoroscopic image sets to accurately reproduce the kinematics of the knee during activities such as stair ascent/descent, gait and weight-bearing flexion-extension. The effects of combined meniscal damage to the ACL-injured knee will be determined directly from the three-dimensional knee models as well. The second aim of this project is to investigate the patients after ACL reconstruction surgery in a long-term follow-up study. To quantify the biomechanical effects of ACL reconstruction and a combined meniscal injury towards the efficacy of ACL reconstruction, the same patients from the first aim will return two times over a three year period, at 6 and 36 months following ACL reconstruction, for additional fluoroscopic imaging. ACL-reconstructed patients will be divided into three groups, those with no meniscal injury, those with medial meniscal tears, and those with lateral meniscal tears. The ACL- reconstructed knees will be tested again during the same in-vivo functional activities performed in the first aim, and 6DOF knee kinematics will be measured. The effect of combined meniscal tear on knee joint kinematics after ACL reconstruction will be analyzed quantitatively. The proposed study is a unique approach to one of the most important clinical problems in Sports Medicine Surgery. Our easy and powerful analysis technique will provide a thorough understanding of the effects of the combined ACL and meniscal injury on the 6DOF in-vivo dynamic knee joint function. The long-term follow up data will further elucidate the efficacy of contemporary ACL reconstruction in restoring normal knee function. This knowledge will lead to an improved patient care, as a guideline can be developed for new ACL reconstruction techniques that more accurately reproduce the normal in-vivo knee kinematics. In restoring the normal physiological functions of the knee joint and thereby preventing long-term joint degeneration, the need for frequent hospital visits, excessive physical therapy, and revision surgery - all inherent to the current practice - could be reduced. PUBLIC HEALTH RELEVANCE. This investigation will measure the six degrees-of-freedom knee kinematics of patients before and after anterior cruciate ligament (ACL) reconstruction in a longitudinal experimental design. The effects of combined meniscal injury on the efficacy of ACL reconstruction will also be analyzed. The knowledge gained from this study will provide a general, quantitative biomechanical guideline for developing new surgical treatments of ACL injuries, thereby restoring long term joint stability and preventing joint degeneration after surgical reconstruction of the injured ACL.